Estrogen replacement therapy has been well established as the treatment of choice in women for the prevention of osteoporosis. C. Christiansen, R. Lindsay, Estrogen, Bone Loss and Preservation, Osteoporosis International, 1, 15-21 (1990)! The downside to this therapy is that when estrogen is given alone i.e. without the opposing effects of progestins, proliferative effects on the uterus may result and thereby can put the patient at risk for endometriosis and/or endometrial cancer. Although less clear, unopposed estrogen replacement therapy has been implicated in increasing the incidence of breast tumor formation. Non-steroidal antiestrogen drugs such as Tamoxifen have been used in the treatment of breast cancer. The drug also is known to increase bone mass, acting as a bone-sparing estrogen agonist in bone while acting as an antagonist in uterine tissue. The drug, however, has been demonstrated to have partial agonist effects in the uterus, which therefore is of some concern. A more recent antiestrogen drug, Lilly's Raloxifene, is a non-steroidal antiestrogen which appears to be more tissue selective. While having the desirable property of sparing bone, it has been demonstrated to stimulate uterine growth in animal models to a lesser degree than Tamoxifen. A review on the tissue selective action of estrogen analogs has recently appeared. G. L. Evans and R. T. Turner, Tissue Selective Actions of Estrogen Analogs, Bone, 17, no. 4, 1815-1905 (1995)!
The compounds described in the present invention are partial estrogen agonists and have potential use in treating osteoporosis, prostatic hypertrophy, breast cancer and endometrial cancer.